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Neurology 2000;54:407
© 2000 American Academy of Neurology
Articles

Cholinergic dysfunction in diseases with Lewy bodies

P. Tiraboschi, MD, L. A. Hansen, MD, M. Alford, BA, M. N. Sabbagh, MD, B. Schoos, DO, E. Masliah, MD, L. J. Thal, MD and J. Corey-Bloom, MD, PhD

From Neurologia Prima (Dr. Tiraboschi), Ospedali Riuniti, Bergamo, Italy; the Department of Neurosciences (Drs. Hansen, Sabbagh, Masliah, Thal, and Corey-Bloom, and M. Alford), University of California, San Diego, La Jolla; and Neurology Service (Drs. Sabbagh, Schoos, Thal, and Corey-Bloom), VA Medical Center, San Diego, CA.

Address correspondence and reprint requests to Dr. Jody Corey-Bloom, Neurology Service (9127), VA Medical Center, 3350 La Jolla Village Dr., San Diego, CA 92161; e-mail: jcoreybl{at}vapop.ucsd.edu

OBJECTIVE: To evaluate cholinergic activity in diseases with Lewy bodies (LB; LB variant of AD [LBV], diffuse LB disease [DLBD], and Parkinson’s disease [PD]) to determine if 1) AD changes are requisite to cholinergic dysfunction, 2) cholinergic activity declines to the same extent in neocortical and archicortical areas, and 3) cholinergic loss is influenced by APOE genotype.

BACKGROUND: Like AD, diseases with LB are associated with decreased choline acetyltransferase (ChAT) activity. Increased APOE {epsilon}4 allele frequency has been reported in LBV. Whether APOE genotype affects cholinergic function in LBV remains unclear.

METHODS: An autopsy series of 182 AD (National Institute on Aging and Consortium to Establish a Registry for Alzheimer’s Disease criteria), 49 LBV, 11 PD, 6 DLBD, and 16 normal control (NC) subjects. APOE genotype and ChAT activity (nmol/h/100 mg) in the midfrontal and hippocampal cortices were determined.

RESULTS: Mean midfrontal ChAT activity was markedly reduced in diseases with LB (LBV: 53.3 ± 39.0; PD: 54.8 ± 35.7; DLBD: 41.3 ± 24.8) compared to NC (255.4 ± 134.6; p < 0.001) and AD (122.6 ± 78.9; p < 0.05). Among diseases with LB, midfrontal ChAT activity was decreased to a similar extent in patients with (LBV) and without (DLBD and PD) AD pathology. Although mean ChAT activity for LBV was less than half that for AD in the midfrontal cortex, it was similar to that for AD in the hippocampus (LBV: 243.5 ± 189.7; AD: 322.8 ± 265.6; p > 0.05). However, hippocampal ChAT activity for both AD and LBV was lower than that for NC (666.5 ± 360.3; p < 0.001). The {epsilon}4 allele dosage did not influence midfrontal ChAT activity in LBV.

CONCLUSIONS: Marked losses in midfrontal ChAT activity occur in diseases with LB, independent of coexistent AD changes. A greater midfrontal, as opposed to hippocampal, cholinergic deficit may differentiate LBV from AD. The lack of a relationship between {epsilon}4 allele dosage and midfrontal ChAT activity suggests that other factors may play a role in its decline in LBV.

Key words: Cholinergic dysfunction—Lewy body disease—APOE—AD




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